Endocrine Abstracts

Craniopharyngiomas are tumours which grow in the region of the sella, with adamantinomatous (ACP) and papillary (PCP) subtypes. While usually ‘benign’, They can have devastating long term sequelae, both from the mass effects of the tumour itself on the visual, pituitary or hypothalamic pathways, but also from the neurosurgical challenge to achieve tumour control with preservation of the surrounding pituitary and hypothalamic pathways. To date there is no satisfactory medical therapy for these tumours. The ACP subtype accounts for 10% of paediatric intracranial tumours. Potential therapies may depend on establishing and exploiting the molecular pathogenesis of these tumours.

Key components of the Wnt signaling pathway have previously shown to play important roles in colorectal, breast, stomach and prostate cancer. Mutations in the β-catenin gene, CTNNB1, have been implicated in the tumorigenesis pathway of ACPs. β-Catenin plays a role in cadherin mediated cell-cell adhesion, and also acts as a signal mediator, functioning as a downstream mediator. It is thought to stabilise and accumulate in the cytosol, translocating to the nucleus and inducing the transcription of the Wnt target genes. Upstream it is linked to membrane cadherins such as E-cadherin, α-catenin, and plakoglobin. These interactions to date not been explored to our knowledge in craniopharyngiomas.

We have examined in a large cohort of 98 craniopharyngiomas, comprising 80 ACPs and 18 PCPs modifications in the Wnt signalling pathway, particularly in β-catenin, helping to separate them as distinct entities. β-catenin was found to be translocated into the nucleus in discrete clusters of tumour cells in all (100%) ACPs, but the gene mutation rate of the β-catenin CTNNB1 gene was only 50%. Further to this, we are currently exploring changes in other parts of the E-cadherin complex of proteins, which may account for the aberrant β-catenin localisation.